A study published in Neuron reveals a previously unknown way in which cannabidiol (CBD) reduces seizures in many treatment-resistant forms of pediatric epilepsy. Researchers at NYU Grossman School of Medicine found that CBD blocked signals carried by a molecule found in neurons called lysophosphatidylinositol (LPI). Neuroscientists believe they amplify nerve signals as part of normal function, but the disease hijacks them, increasing seizure activity.
The study confirmed a previous finding that CBD lessens LPI’s ability to intensify nerve signals in the hippocampus. The findings also showed that LPI also weakens signals that counter seizures.
The study results build on how each neuron “fires” to transmit an electrical pulse down to a synapse. When it reaches the cell’s end before the synapse, the pulse causes the release of compounds called neurotransmitters. When the neurotransmitters cross the synaptic gap, the signals either encourage the cell to fire (excitation) or prohibit firing (inhibition). Balance between the signals is critical to normal brain function. Otherwise, excitation results in seizures.
This study confirmed findings from previous studies that LPI influences nerve signals by binding to the G-coupled receptor 55 (GPR55), a protein found on neuron cell surfaces. LPI-GPR55 presynaptic interaction releases calcium ions within the cell, prompting cells to release the main excitatory neurotransmitter, glutamate. When LPI activates GPR55 on the other side of the synapse, it weakens inhibition by hindering the supply and optimal arrangement of proteins necessary for inhibition. The study authors call the result a “dangerous” two-pronged mechanism to increase excitability.
The research team found that either genetically engineering mice to lack GPR55 or giving mice CBD before seizure-inducing stimuli blocked LPI-mediated effects on both excitatory and inhibitory synaptic transmission. They believe CBD blocks a “positive feedback loop” in which seizures increase LPI-GPR55 signaling, and this loop encourages more seizures and consequently increases levels of both LPI and GPR55. This finding offers insights into mechanisms involved in recurring epileptic seizures and potential drug treatments for retractable epilepsy.
Sources: Eureka News Alert, Neuron
